Parasites constitute a major problem in animal husbandry. Most animals suffer from free-flying parasites such as mosquitos, horn flies and stable flies; crawling ectoparasites such as lice, ticks, fleas and mites, burrowing parasites such as bots and grubs, as well as microscopic endoparasites such as coccidia, worms and the like. Several methods for partial control of such parasites are known. For example, free-flying parasites such as flies can be marginally controlled by standard methods such as air-dispersed and contact insecticides and fly traps. Intestinal parasites are typically controlled by periodic de-worming, for instance by tube worming in the case of equine. Skin-inhabiting and crawlingparasites and usually controlled by drenching, washing, or spraying the animals with appropriate parasiticides. Many of the available treatments require the use of extremely toxic substances, for example organophosphates, and heavy metal preparation such as arsenic and mercury formulations.
A major problem exists in the treatment of parasites in domestic animals which are allowed to roam freely over a specified area. For example, animals such as cattle and sheep, which are raised for their human food and clothing products, are often permitted to feed and grow on open grassland, particularly during warm weather grass growing seasons. Also, because herds of such animals are often rather large, individual treatment at short intervals is economically prohibitive. Consequently, such animals are not subject to normal methods of controlling parasites.
Additionally, many parasites, including mosquitoes, lice, mites and the like, lay eggs on an animal, and the eggs hatch within about twenty one days. The only way to destroy the repeating crops of parasites is to have repeated treatments of spraying or drenching, or alternatively to have a continuous supply of an effective amount of a parasiticide in the blood stream of an animal for a prolonged period following a single adminstration.
The idea of prolonged release formulations for the continuous delivery of an active agent to an animal system over a predetermined period of time is known. For example, Siegrist et al. in U.S. Pat. No. 3,535,419, disclose sustained release veterinary compositions useful for ruminant fertility control. As pointed out by Siegrist et al., the current state of development of such sustained release formulations suffers in so many respects that widespread use is precluded. In particular, slow release implants suffer from leaving unwanted residues following payout of the active ingredient, as well as failing to afford sufficiently sharp and consistent endpoints to be predictable.
Reuter et al., in U.S. Pat. No. 4,011,312, describe what is said to be a prolonged release drug dosage form useful for the treatment of bovine mastitis. Such formulation comprises an antimicrobial agent dispersed in a matrix of a low molecular weight polyester of glycolic and lactic acids. The polyester utilized is required to contain about 60 to 80 mole percent of glycolic acid and 20 to 40 mole percent of lactic acid, with a molecular weight of less than 2000. Such formulations are said to provide effective medication for up to four to six weeks.
Moreover, many prior art compositions suffer from leaving unwated residues upon dissolution of the copolymer matrix. This is of utmost importance when the compositions are to be used in animals raised for human food production. Moreover, since many chemical compounds which are effective against diseases at certain dose levels can be lethal to the host animal when administered in excessive amounts, it is imperative that a controlled release formulation be one that does not expose the host animal to lethal doses.
An object of the present invention is to provide a unique formulation of a parasiticide combined with a copolymer of lactic acid and glycolic acid such that the active agent is controllably released and total biodegradation of the copolymeric matrix is achieved with no unwanted residue remaining in the animal tissue. A further object is to provide a formulation which is capable of systemically providing uniform protection against endoparasites for a predetermined period of time.